Bioseparation EngineeringIntroduction

Biotechnologybuilt on the genetic manipulation of organisms to produce commercial products or processes

Biochemical Engineeringresponsible for the implementation of the products and processes

Two Disciplines of Biochemical Engineering

Upstream Engineering (Fermentation)Downstream Engineering (Bioseparation or Purification)

Figure 1. Relation between starting product concentration in completed broth or medium, and final selling price of the prepared product (Dwyer JL, 1984).

Figure 2. Primary factors affecting separation vs. particle size (Atkinson B and Mavituna F, 1983)

Separation Process Design

• mimic/similar process/case• new concept process• yield and purity• cost of production• scalability (scale-up, scale-down)•Easy maintenance

Separation Process Synthesis

Approaches must be made if future scale-up is in mind*design software*information from equipment vendor

Separation Process Synthesis

Ex : Penicillin Production

Figure 3. Penicillin production. After fermentation the biomass is separated by filtration. The antibiotic, which is in the filtrate, is isolated and purified by extraction. It is then polished by crystallization and dried.

Separation Process Synthesis

Vacuum Filter

Increasing amount of washing water increases recoverybut thus the amount of wastewater generated

Extraction

Temperature: material degradation and yieldSolvent: type of solvent, solvent to water ratioMode of Operation: Single or multiple stage

Optimization of operating condition is essential!!

Are there other novel concepts of separation???

Separation Process Synthesis

Microfiltration Ultrafiltration Reverse OsmosisBroth Product

(Penicillin G)

Biomass Solvent

Figure 4. Possible alternative scheme for penicillin purification.

Ex : Spray drying

Spray Dryer

Air: flowrate, temperature, moisture contentSlurry: physical properties, feed rate, moisture content

- Drying Efficiency: moisture content, powder in vent air

Multiple Input Multiple Output (MIMO) problemwith interaction

Criteria for Process Synthesis

• product value, purity, impurities acceptable• cost of production as related to yield• scalability• robustness with respect to process stream variables•Alternative process/technology

Used in evaluating and designing a bioseparation process

Stages of Bioseparation: An idealized process(1)removal of solids (or recovery), (2)isolation of product, (3)purification,

and (4)polishing constitute a sequence of events applied to nearly every product preparation

Stage Objective(s) Typical Unit OperationsSeparation of insolubles

Remove or collect cells, cell debris, or other particulatesReduce volume (depends on unit operation)

Filtration, sedimentation, extraction, adsorption

Isolation of product Remove materials having properties widely different from those desired in productReduce volume (depends on unit operation)

Extraction, adsorption, ultrafiltration, precipitation

Purification Remove remaining impurities, which typically are similar to the desired product in chemical functionality and physical properties

Chromatography, affinity methods, crystallization, fractional precipitation

Polishing Remove liquidsConvert the product to crystalline form (not always possible)

Drying, crystallization

Table 1. Objectives and Typical Unit Operations of the Four Stages in Bioseparation (Harrison et al., 2003)

• Intracellular, extracellular product• Fermentation – broth components• In situ separation with fermentation (Ex : ethanol, antibiotics, taxol)• Separation for next step (Ex : lactic acid for polymer)